Radiosensitising effect of electrochemotherapy with bleomycin in LPB sarcoma cells and tumors in mice

BACKGROUND: Bleomycin is poorly permeant but potent cytotoxic and radiosensitizing drug. The aim of the study was to evaluate whether a physical drug delivery system – electroporation can increase radiosensitising effect of bleomycin in vitro and in vivo. METHODS: LPB sarcoma cells and tumors were treated either with bleomycin, electroporation or ionizing radiation, and combination of these treatments. In vitro, response to different treatments was determined by colony forming assay, while in vivo, treatment effectiveness was determined by local tumor control (TCD(50)). Time dependence of partial oxygen pressure in LPB tumors after application of electric pulses was measured by electron paramagnetic oxyimetry. RESULTS: Electroporation of cells in vitro increased radiosensitising effect of bleomycin for 1.5 times, in vivo radiation response of tumors was enhanced by 1.9 fold compared to response of tumors that were irradiated only. Neither treatment of tumors with bleomycin nor application of electric pulses only, affected radiation response of tumors. Application of electric pulses to the tumors induced profound but transient reduction of tumor oxygenation. Although tumor oxygenation after electroporation partially restored at the time of irradiation, it was still reduced at the level of radiobiologically relevant hypoxia. CONCLUSION: Our study shows that application of electric pulses to cells and tumors increases radiosensitising effect of bleomycin. Furthermore, our results demonstrate that the radiobiologically relevant hypoxia induced by electroporation of tumors did not counteract the pronounced radiosensitising effect of electrochemotherapy with bleomycin

Electrotransfer of Single-Stranded or Double-Stranded DNA Induces Complete Regression of Palpable B16.F10 Mouse Melanomas

Enhanced tumor delivery of plasmid DNA with electric pulses in vivo has been confirmed in many preclinical models. Intratumor electrotransfer of plasmids encoding therapeutic molecules has reached Phase II clinical trials. In multiple preclinical studies, a reduction in tumor growth, increased survival or complete tumor regression have been observed in control groups in which vector or backbone plasmid DNA electrotransfer was performed. This study explores factors that could produce this antitumor effect. The specific electrotransfer pulse protocol employed significantly potentiated the regression. Tumor regression was observed after delivery of single-stranded or double-stranded DNA with or without CpG motifs in both immunocompetent and immunodeficient mice, indicating the involvement of the innate immune system in response to DNA. In conclusion, this study demonstrated that the observed antitumor effects are not due to a single factor, but to a combination of factors

Influence of bedding and backfill soil type on deformation of buried sewage pipeline

In the paper, the influence of different types of bedding and backfill soil surrounding underground sewage duct on its deformation was analysed. Impact of increased soil lateral pressure was examined by considering the construction of an embankment nearby the underground pipeline. Numerical computations of three different variants of bedding and backfill soil surrounding the pipe were carried out. Displacements and deformation of the pipe were calculated using the finite element method with adoption of elastic-perfectly plastic constitutive model of soil. Subsequent stages of the construction were taken into account. Shear strength reduction method was applied to evaluate the factor of safety of the entire system. Finally, the results and conclusions were depicted

The effect of the histological properties of tumors on transfection efficiency of electrically assisted gene delivery to solid tumors in mice

Uniform DNA distribution in tumors is a prerequisite step for high transfection efficiency in solid tumors. To improve the transfection efficiency of electrically assisted gene delivery to solid tumors in vivo, we explored how tumor histological properties affected transfection efficiency. In four different tumor types (B16F1, EAT, SA-1 and LPB), proteoglycan and collagen content was morphometrically analyzed, and cell size and cell density were determined in paraffin-embedded tumor sections under a transmission microscope. To demonstrate the influence of the histological properties of solid tumors on electrically assisted gene delivery, the correlation between histological properties and transfection efficiency with regard to the time interval between DNA injection and electroporation was determined. Our data demonstrate that soft tumors with larger spherical cells, low proteoglycan and collagen content, and low cell density are more effectively transfected (B16F1 and EAT) than rigid tumors with high proteoglycan and collagen content, small spindle-shaped cells and high cell density (LPB and SA-1). Furthermore, an optimal time interval for increased transfection exists only in soft tumors, this being in the range of 5-15 min. Therefore, knowledge about the histology of tumors is important in planning electrogene therapy with respect to the time interval between DNA injection and electroporation

Datasets: Dietary Carbon Incorporation in Ichthyocarbonate

Datasets Dietary Carbon Incorporation in Ichthyocarbonate.zip contains: Mendeley-Ichthyocarbonate.csv Mendeley-DaysPastFeeding-C.csv Mendeley-DaysPastFeeding-MgCO3.csv Mendeley-Diet.csvDatasets accompanying manuscript accepted for publication in Science of the Total Environment. Manuscript is titled: Implications of dietary carbon incorporation in fish carbonates for the global carbon cycle. Datasets include: 1. Mendeley-Ichthyocarbonate.csv: Presents ichthyocarbonate compositional characteristics, including stable carbon isotope values of the carbonate and associated organic matter, %TOC, and %carbonate (NM stands for not measured). 2. Mendeley-DaysPastFeeding-C.csv: Presents stable carbon isotope values of ichthyocarbonate measured in successive days since last meal, 3. Mendeley-Dietcsv: Presents compositional characteristics of diet fed to experimental fish, and 4. Mendeley-DaysPastFeeding.csv: Presents d-spacing and mol%MgCO3 calculated from results of XRD analyses.Peer reviewe